Perinuclear theca protein FNDC8 interacts with CCIN and ACTL7A to ensure proper sperm head shaping during spermiogenesis

Precise shaping of the sperm head is essential for successful fertilization, and defects in this process are frequently associated with severe forms of male infertility. Sperm head morphology is coordinated by several testis-specific structures, including the apical ectoplasmic specialization (ES), manchette, and perinuclear theca (PT)—a dense cytoskeletal layer that envelops the nucleus during spermiogenesis. However, the molecular components and physiological functions of the PT remain incompletely understood. This study identified FNDC8 as a testis-enriched protein primarily localized to the PT. Genetic disruption of FNDC8 resulted in male infertility characterized by spermatozoa exhibiting acrosome detachment from the nuclear membrane and sperm head surface collapse. FNDC8 interacted with CCIN and ACTL7A during spermiogenesis, and its depletion destabilized both proteins. Together, these results indicate that FNDC8 is integral to the structural integrity of the PT by mediating protein interactions critical for sperm head morphogenesis, implicating FNDC8 dysfunction as a potential contributor to teratozoospermia in humans.